Obesity is a central feature of the metabolic syndrome, which leads to significant morbidity and mortality by increasing the risk of diabetes and cardiovascular disease. The absorption of dietary triglycerides with subsequent storage in adipose tissue is a key step in the development of obesity (Berk, P. D., et al., J Biol Chem 274, 28626-28631 (1999); Berk, P. D., et al., J Biol Chem 272, 8830-8835 (1997)). Under physiological conditions, cellular uptake of fatty acids occurs primarily through protein-mediated pathways consisting of a number of fatty acid transporters expressed in tissue-specific patterns (Stump, D. D., Fan, X. & Berk, P. D., J Lipid Res 42, 509-520 (2001); Anderson, C. M. & Stahl, A., Mol Aspects Med 34, 516-528 (2013)). Translocation of these transporters from the cytosol to the cell membrane is the major mechanism through which the rate of fatty acid uptake can be acutely regulated in response to dietary and metabolic cues (Stahl, A. et al., Developmental cell 2, 477-488 (2002); Luiken, J. J., et al., Am J Physiol Endocrinol Metab 282, E491-495 (2002); Luiken, J. J., et al., Diabetes 52, 1627-1634 (2003)). Fatty acid transporter translocation is regulated systemically by hormones and locally by muscle contraction (Stahl, A. et al., Developmental cell 2, 477-488 (2002); Luiken, J. J., et al., Am J Physiol Endocrinol Metab 282, E491-495 (2002); Luiken, J. J., et al., Diabetes 52, 1627-1634 (2003)).
Mfge8 is an integrin ligand (Hanayama, R., et al., Nature 417, 182-187 (2002)) that is highly expressed in the adipose tissue of mice on a high-fat diet (HFD) (Aoki, N. et al., Endocrinology 148, 3850-3862 (2007)). Both the expression of Mfge8 and the integrin receptors for Mfge8 are increased in the adipose tissue of obese humans (Henegar, C. et al., Genome Biol 9, R14 (2008)).